Mats Bue1, Tomás Sou2, Anna Sophie L Okkels3, Pelle Hanberg4, Anders Thorsted5, Lena E Friberg6, Torben L Andersson7, Kristina Öbrink-Hansen8, Steffen Christensen9. 1. Department of Orthopaedic Surgery, Horsens Regional Hospital, Sundvej 30, 8700 Horsens, Denmark; Department of Anaesthesia and Intensive Care Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark; Orthopaedic Research Unit, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark. Electronic address: matsbue6@rm.dk. 2. Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 751 24 Uppsala, Sweden. Electronic address: tomas.sou@farmaci.uu.se. 3. Department of Anaesthesia and Intensive Care Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark. Electronic address: asokkels@hotmail.com. 4. Department of Orthopaedic Surgery, Horsens Regional Hospital, Sundvej 30, 8700 Horsens, Denmark; Orthopaedic Research Unit, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark. Electronic address: pehanb@rm.dk. 5. Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 751 24 Uppsala, Sweden. Electronic address: anders.thorsted@farmbio.uu.se. 6. Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 751 24 Uppsala, Sweden. Electronic address: lena.friberg@farmbio.uu.se. 7. Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark. Electronic address: t.l.a@stofanet.dk. 8. Department of Infectious Diseases, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark. Electronic address: kristina.Obrink.Hansen@auh.rm.dk. 9. Department of Anaesthesia and Intensive Care Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark. Electronic address: steffen.christensen@auh.rm.dk.
Abstract
OBJECTIVES: Piperacillin is a β-lactam antimicrobial frequently used in critically ill patients with acute kidney injury treated with continuous renal replacement therapy (CRRT). However, data regarding piperacillin tissue concentrations in this patient population are limited. A prospective observational study was conducted of free piperacillin concentrations during a single 8-h dosing interval in plasma (8 samples) and subcutaneous tissue (SCT) (13 samples), in 10 patients treated with CRRT following piperacillin 4 g given every 8 h as intermittent administration over 3 min. METHODS: A population pharmacokinetic model was developed using NONMEM 7.4.3, to simulate alternative administration modes and dosing regimens. SCT concentrations were obtained using microdialysis. Piperacillin concentrations were compared to the clinical breakpoint minimum inhibitory concentration (MIC) for Pseudomonas aeruginosa (16 mg/l), with evaluation of the following pharmacokinetic/pharmacodynamics targets: 50% fT > 1 × MIC, 100% fT > 1 × MIC, and 100% fT > 4 × MIC. RESULTS: SCT concentrations were generally lower than plasma concentrations. For the target of 50% free time (fT) > 1 × MIC and 100% fT > 1 × MIC, piperacillin 4 g every 8 h resulted in probability of target attainment (PTA) >90% in both plasma and SCT. PTA > 90% for the target of 100% fT > 4 × MIC was only achieved for continuous infusion. CONCLUSIONS: Piperacillin 4 g every 8 h is likely to provide sufficient exposure in both plasma and SCT to treat P.aeruginosa infections in critically ill patients on CRRT, given that targets of 50% fT > 1 × MIC or 100% fT > 1 × MIC are adequate. However, if a more aggressive target of 100% fT > 4 × MIC is adopted, continuous infusion is needed.
OBJECTIVES:Piperacillin is a β-lactam antimicrobial frequently used in critically illpatients with acute kidney injury treated with continuous renal replacement therapy (CRRT). However, data regarding piperacillin tissue concentrations in this patient population are limited. A prospective observational study was conducted of free piperacillin concentrations during a single 8-h dosing interval in plasma (8 samples) and subcutaneous tissue (SCT) (13 samples), in 10 patients treated with CRRT following piperacillin 4 g given every 8 h as intermittent administration over 3 min. METHODS: A population pharmacokinetic model was developed using NONMEM 7.4.3, to simulate alternative administration modes and dosing regimens. SCT concentrations were obtained using microdialysis. Piperacillin concentrations were compared to the clinical breakpoint minimum inhibitory concentration (MIC) for Pseudomonas aeruginosa (16 mg/l), with evaluation of the following pharmacokinetic/pharmacodynamics targets: 50% fT > 1 × MIC, 100% fT > 1 × MIC, and 100% fT > 4 × MIC. RESULTS: SCT concentrations were generally lower than plasma concentrations. For the target of 50% free time (fT) > 1 × MIC and 100% fT > 1 × MIC, piperacillin 4 g every 8 h resulted in probability of target attainment (PTA) >90% in both plasma and SCT. PTA > 90% for the target of 100% fT > 4 × MIC was only achieved for continuous infusion. CONCLUSIONS:Piperacillin 4 g every 8 h is likely to provide sufficient exposure in both plasma and SCT to treat P.aeruginosa infections in critically illpatients on CRRT, given that targets of 50% fT > 1 × MIC or 100% fT > 1 × MIC are adequate. However, if a more aggressive target of 100% fT > 4 × MIC is adopted, continuous infusion is needed.
Authors: Elisabeth Krogsgaard Petersen; Pelle Hanberg; Martin Knudsen; Sara Kousgaard Tøstesen; Andrea René Jørgensen; Kristina Öbrink-Hansen; Kjeld Søballe; Maiken Stilling; Mats Bue Journal: Antibiotics (Basel) Date: 2022-07-07
Authors: Daniel J Selig; Jesse P DeLuca; Kevin K Chung; Kaitlin A Pruskowski; Jeffrey R Livezey; Robert J Nadeau; Elaine D Por; Kevin S Akers Journal: J Clin Pharm Ther Date: 2022-03-29 Impact factor: 2.145